John P. Curran, MD, and Farouk L. Al-Salihi, MD

ABSTRACT. A
massive outbreak of the staphylococcal scalded skin syndrome
due to an organism with an unusual phage pattern, occurred
during a 115-day period and involved 68 newborns. Generalized
exfoliative dermatitis was seen in 24 babies, and
Staphylococcus aureus was isolated from 23. Fourteen
isolates were phage typed, with 13 reported as the epidemic
strain 29/79/80/3A/3C/54/75. Eight babies had generalized
scarlatiniform eruption without exfoliation (staphylococcal
scarlet fever). Cultural data were available from six, all
positive for S. aureus. Four organisms were typed and
reported as the epidemic strain. Of 34 infants with bullous
impetigo 20 had cultures that were positive for S.
aureus, and four were phage typed, revealing the epidemic
strain. Illness was mild in all patients; there were no
deaths and no invasive forms of staphylococcal infection.
The male to female ratio of generalized
exfoliative disease was 5:1. The concept of a neonatal
staphylococcal scalded skin syndrome, comprised of a triad of
skin disorders induced by an exotoxin elaborated by certain
strains of coagulase positive S. aureus, is confirmed.
Pediatrics 66:285-290, 1980; scalded skin syndrome,
staphylococcal disease, toxic epidermal necrolysis,
exfoliative dermatitis, impetigo

Staphylococcal scalded skin syndrome (SSSS)
typically occurs as isolated cases, occasionally in small
clusters, with the largest epidemic previously reported
consisting of 8 patients.1 The
purpose of this paper is to describe a massive outbreak of
the disorders comprising the “expanded”
staphylococcal scalded skin syndrome2 that involved 68 newborns due to an
epidemic strain (ES) organism with an unusually phage
pattern.

DESCRIPTION OF EPIDEMIC

The year of the outbreak 6,000 newborns were
delivered at Margaret Hague Maternity Hospital, Jersey City,
NW. The newborn units consisted of five regular nurseries,
each containing 25 bassinets: Nursery 4 South (N4S), Nursery
4 Central (N4C), Nursery 4 North (N4N), and Nursery 5 South
(N5S). An isolation unit (IU) with 20 bassinets was located
on the 6th floor, along with a Premature Unit.

Between March 22 and April 3, three cases of
exfoliative dermatitis occurred in N4S. Penicillin-sensitive
coagulase-positive Staphylococcus aureus was cultured
from swabs of the nose, eyes, and skin of these babies.
During the same period, two newborns were seen in clinic
vesicobullous impetigo. No cases of staphylococcus infection
were seen for the next 17 days, until April 20 when three
newborns with erythema, exfoliation, and positive
Nikolsky’s sign were admitted to the IU from the
clinic. This signalled an acceleration of cases of
staphylococcal skin disease from N4S, and 60 cases were seen
from April 20 to June 20. The last case of exfoliative skin
disease was seen on June 20, followed by three scattered
cases of bullous impetigo, the last on July 14, terminating
the outbreak. The epidemic encompassed a period of 115 days
and involved 68 cases of three variants of the neonatal SSSS
in babies 4 to 15 days old.

MANAGEMENT OF OUTBREAK

Beginning on May 29, intensive bacteriologic
surveys were made of cultures from newborns, personnel, and
the nursery environment. On June 6 N4S was closed for six
weeks, scrubbed and repainted. All newborns were bathed once
daily with a 3% hexachlorophene preparation (pHisoHex,
Winthrop Laboratories) and a
polymycin-B-bacitracitin-neomycin ointment (Neosporin
ointment, Burroughs Wellcome Co) was applied to the nares,
axillae, and umbilical stumps. Mothers were instructed to
continue daily hexochlorophene bathing and told to report any
skin rash or illness in the babies or other family
members.

CLINICAL FINDINGS

The 68 patients in this report all were seen
with one of the disorders comprising the triad of the
expanded scalded skin syndrome:2
(1) generalized exfoliative disease (Ritters), (2)
generalized scarlatiniform eruption without exfoliation
(staphylococcal scarlet fever), and bullous impetigo. Among
the 68 babies, only five had other forms of infection due to
the epidemic strain—four had purulent conjunctivitis
and one had breast abscess. All five of these patients had
generalized exfoliative disease. There were no cases of
sepsis, pneumonia, septic arthritis, meningitis, omphalitis,
cellulitis, or furunculosis.

Generalized Exfoliative Disease

Fig 1.A
newborn with generalized exfoliative disease.

The clinical features of generalized
exfoliative disease (Table) corresponded closely to the
description by Rittershain and others.1-30 The signs and clinical course of
the disease were similar in the 26 infants, who ranged in age
from 4 to 14 days. Onset was abrupt, with erythema, often
first visible on the face, that involved the entire body
within 24 hours. The ereythema blanched with pressure, and in
many babies the skin was tender to touch. Within 24 to 48
hours the skin became wrinkled, or flat bullae containing
clear fluid appeared in various locations, most commonly the
face, distal extremities, and diaper area. (Fig 1). Over a
period of two or three days the skin exfoliated in large
sheets, exposing a red moist surface. The most denuded areas
dried rapidly, soon appearing hyperkeratotic, with
desquamation of large flakes for several days (Fig 2). The
erythematous areas that did not exfoliate showed coarse
desquamation for as long as ten days. The skin appeared
normal ten to 14 days after onset. The number, size, and
distribution of the areas of exfoliation varied. In nine
infants exfoliation was generalized, and four of these
patients were among the most toxic in the series. The face
was involved in 22, the trunk in 20 and the extremities in 12
infants. Exfoliation was often distal on the extremities,
involving limited, well-demarcated areas such as the heel.
(Fig 3). No mucous membrane lesions were seen. Fever was not
a remarkable feature; as observed in only 11 infants, fever
was mostly low grade and transient, lasting 48 hours or less
in seven of the infants. Two babies had elevation to 104 F
(rectal), one for 24 hours and the other for 48 hours. Both
of these patients experienced transient diarrhea. A single
newborn had a low grade fever for six days, but showed no
other signs of systemic disease. For the most part,
generalized exfoliative disease was a mild, uncomplicated
disorder. There were no deaths. While several of the infants
appeared irritable during the periods of erythema and
exfoliation, most showed no other signs of illness. Two
patients developed deep, ulcerative lesions at sites of
exfoliation, on on the heel (Fig 3), the other on the knee.
The latter required skin grafting. Only two infants were
anorectic and received intravenous fluids, both with
generalized exfoliation and a prolonged course. A
hospitalized baby developed tetany. Four patients had
purulent conjunctivitis, but the ES organism was obtained
from the conjunctival sacs of four others who did not develop
clinically apparent eye infection. One breast abscess
required incision and drainage. The male
to female ratio of exfoliative disease was 5.5:1. Of
the 26 babies, exfoliation was less than generalized in 17,
commonly involving the face, or the acral areas, with
exfoliation of large sheets of skin from the glove or sock
areas.

TABLE. Clinical features in 68 Newborns with SSSS

Manifestation

No. of
Cases

%
of Total

Dequamation

42

62

Generalized erythema

34

50

Exfoliation, localized

17

25

Fever

11

16

Exfoliation, generalized

17

25

Conjunctivitis

4

6

Diarrhea, transient

2

3

Skin ulceraton

2

3

Anorexia

2

3

Breast Abscess

1

1.5

Tetany

1

1.5

Fig 2.A
12-day-old baby with exfoliative disease of three days
duration,
with maximum involvement of the face.

Fig 3A
10-day-old baby with localized exfoliation of the distal
extremities
with ulceration of the heel. Note the rolled margins of
exfoliating skin.

Generalized Scarlatiniform Eruption without
Exfoliation

Generalized scarlatiniform eruption without
exfoliation was observed in eight newborns. All were afebrile
and showed no signs of illness other than generalized
erythema, with no lysis of the epidermis. The rash resembled
streptococcal scarlet fever, including non-blanching
accentuation of the erythema in the flexion creases.
Pharyngitis, cervical adenitis, strawberry tongue, or palatal
petechiae were not seen. Nikolsky’s sign was negative.
Healing was by coarse desquamation over a period of five or
ten days. The male to female ration was 1.5:1. The
designation generalized scarlatiniform exfoliation seems more
appropriate than scarlet fever, since the other signs of
scarlet fever (most notably fever) were not present in the
staphylococcal illnesses in this series.

Bullous Impetigo

Bullous impetigo was noted in 34 babies. The
bullae were small, flaccid, and well-demarcated, and
contained clear or cloudy yellow fluid. The skin between
lesions appeared normal. All infants were afebrile and
otherwise well, but several observers noted a faint transient
erythema of the face in some patients. Recovery was rapid,
the lesions resolving over three to five days, with fine
desquamation noted in eight infants. The male to female ratio
was 1:1.

Treatment consisted of debriding the
separated skin and cleansing with a 3% hexochlorophen sudsing
emulsion (pHisoHex) three times daily. After careful rinsing
with tap water, the skin was dried and an antibiotic ointment
(Neosporin ointment) was applied to denuded areas. Systemic
antibiotics, notably penicillin and nafcillin, or penicillin
and kanamycin, and later, when the nature of the illness was
recognized and the organism identified as sensitive,
penicillin alone, were administered for a minimum of ten
days. Topical or systemic steroids were not used. A total of
41 babies were admitted, 222 of 26 with scarlatiniform
eruption and 11 of 34 with bullous impetigo.

LABORATORY FINDINGS

White blood cell counts, hematocrits, and
urinalyses were normal, as were chest radiographs of all
inpatients. Cultures were obtained from various sites in 50
of the 68 infants. Staphylococcus aureus, coagulase
positive, were isolated, usually from several sites, from 23
of the 24 babies with generalized exfoliative disease
cultured. But the ES organism was obtained from exfoliating
skin sites in only ten of those infants. Fourteen of the
coagulase-positive organisms were submitted for phage typing,
and 13 were reported as 29/79/80/3A/3C/54/75, an unusual
pattern not previously noted in cases of SSSS. One organism
was type 53, a gourp III phage type not previously associated
with SSS and probably not the causative mechanism in this
case. Of the eight infants with scarlatiniform eruption
without exfoliation, cultural data was available from six,
all positive for S. aureus from sites other than the
skin (nose, throat, eye, umbilical stump). Four of the
organisms were typed and all were reported as the ES. Of the
34 patients with bullous impetigo, 20 cultures were taken and
all were positive for coagulase-positive S. aureus.
The organisms were obtained from the skin lesions in all.
Four were typed and all revealed the ES pattern. Of the 68
patients, cultural data were available from 50, and a
coagulase-positive S aureus was obtained from 48. Twenty-two
of the organisms were phage typed and 21 were
29/79/80/3A/3C/54/75.

DISCUSSION

The association of phage group II
staphylococci with three skin disorders in neonates and young
infants, less commonly in older children, and rarely in
adults,35,36 has been
established. The triad of dermatologic manifestations, termed
the expanded scalded skin syndrome by Melish and
Glasgow,2 includes generalized
exfoliative disease, generalized scarlatiniform eruption
without exfoliation and bullous impetigo. A number of
studies22, 37-42 have identified an extracellular
protein toxic produce from group II staphylococci that
induces cleavage within the granular layer of the epidermis
and exfoliation of the skin of newborn mice that is
indistinguishable from that seen in human patients.39

Review of the literature reveals a variety
of phage patterns associated with SSSS in neonates, infants,
and children, with members of group II almost always present,
and phages 71, 55, 3c and 3A predominant. Of the 26 reported
types, members from group I were present in six, with phages
from III in seven patterns. The epidemic strain in this
report was lysed by the largest group of phages, with
representatives in all three groups. When antibiotic
sensitivities were reported in previous series, there was a
predominance of strains resistant to penicillin (10:6).

The present report confirms the concept of
Melish and Glasgow2 of an
expanded staphylococcal skin syndrome, and demonstrates that
the three variants can occur in a large outbreak caused by
one epidemic strain. Whereas bullous impetigo is a common
manifestation of skin infection by a variety of
staphylococcal types in neonates, Margileth’s statement
that bullous impetigo “should not be included in the
SSSS”29 is refuted by the
evidence presented in this report that the three disorders
are related clinically and etiologically.

The preponderance of
males with generalized exfoliative disease (5:1) suggests
that the circumcision wound may provide a site of
colonization for staphylococci that would result in an
increased incidence of SSSS in males.43 This is not supported by our male to
female ratios of 1.3:1 and 1:1 for scarlatiniform eruption
and bullous impetigo.

Steroids were not administered to any of the
infants. Rudolph et al.28
reported rapid progression of generalized exfoliative disease
in babies who were initially treated with steroids. While
there is no evidence that steroids influence the action of
the exotoxin on the skin, they may interfere with the
host’s inflammatory response to the organisms,
enhancing the production of toxin, and, perhaps, the
invasivness of the bacteria.

Rasmussen44
reported 112 negative blood cultures from 83 patients with
the staphylococcal scalded skin syndrome, and concluded that
the organisms were noninvasive, proliferating on skin and
mucous membranes only, and that the course of the disease was
not altered by administration of antibiotics. Rudolph et
al28 concluded from their
series that appropriate antibiotic therapy resulted in rapid
resolution of the signs and symptoms of SSSS. In the present
series, blood cultures were obtained from 41 patients (22
with exfoliative disease, eight with scarlatiniform eruption,
and 11 with bullous impetigo); the ES was isolated from one,
the youngest infant in the outbreak, who developed
exfoliative disease on day four and experienced a mild
illness without fever or other signs of systemic disease. Our
experience corresponds with that of Rasmussen,44 and suggests that the organisms that
produce SSSS are usually noninvasive and that antibiotic
therapy is probably not helpful in most cases. However, in
reported cases the virulence of the organism varies, as does
the ability of individual infants to localize the infection
and tolerate the effects of liberated toxin. Also,
administration of antibiotic will minimize hospital and
community spread of the bacteria. At his stage of our
knowledge, it would seem wise to treat newborns with SSSS
with systemic antibacterials, based on cultural and
sensitivity data. Margileth29
recommends that a penicillinase-resistant penicillin should
be given to infants under 1 year of age, pending results of
the bacteriologic studies.

[CIRP Note: This report was prepared in 1979
and published in 1980. It appears that the authors were not
completely convinced at that time that the circumcision wound
is a portal of entry for the Staphylococcus aureus
pathogen in circumcised boys. Later studies have firmly
established that the circumcision wound is a portal of entry
for the Staphylococcus aureus pathogen. Today, one may
be confident that open circumcision wound greatly increases
the incidence of staphylococcus infection in newborn boys who
are circumcised.]

SPECULATION AND RELEVANCE

This report confirms the concept of an
expanded staphylococcal scalded skin syndrome comprised of
three disorders with a common etiology, and it demonstrates
that the three can occur together in a single outbreak. The
factors that determine which variety of SSSS will manifest
are unknown. The male to female ratio of
generalized exfoliative disease was 5.5:1, while the male to
female ratios of scarlatiniform eruption and bullous impetigo
were 1.5:1 and 1:1 respectively. We speculate that the three
variants represent differences in the severity of the disease
that are largely determined by the amounts of exotoxin that
are produced and absorbed, and the latter depends not only on
the number, but also on the types of body sites that are
colonized (intact skin, mucous membranes, wounds). Localized
skin involvement results in the mildest form, bullous
impetigo, whereas mucous membrane colonization produces
generalized scarlatiniform eruption. The circumcision wound
is a site conducive not only to rapid bacterial growth, but
also to rapid absorption of exotoxin, and this could account
for the strikingly higher incidence of the severest form,
generalized exfoliative disease, in male newborns.

Significant features of the reported
epidemic are (1) the large numbers of patients with a disease
that usually occurs as isolated cases or small clusters, (2)
the mildness of the disease in all patients, (3) the absence
of invasive forms of the disease and scarlatiniform eruption,
and (5) the high incidence of localized exfoliation.

Rasmussen and Koblenzer45 reported a dramatic increase in the
incidence of SSSS. It is possible that
new strains, with greater virulence, will emerge as causative
organisms in future outbreaks. With our present
knowledge of the clinical features of pathogenisis of SSSS,
prompt recognition and effective management are possible.

ACKNOWLEDGEMENT

We are indebted to Dr Peter Smith, Center
for Disease Control, Atlanta, for the phage typing.